The vascular microenvironment and its stem cells regulate vascular homeostasis

Figures

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  FIGURE 1. The function of the vascular microenvironment. The maintenance, activation and remodeling of the vascular microenvironment regulate the function of neurons, immune, tumor, liver, and spleen cells, and involved in the processes of bone marrow hematopoietic activity, liver regeneration and repair, regulation of neural stem cell function, atherosclerotic (AS) inflammatory response, and pathological vascular remodeling.

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  FIGURE 2. The composition of the vascular microenvironment. The vascular microenvironment can be subdivided into three sections according to the vascular anatomy, from the inside out. The vascular endothelial microenvironment is centered on the vascular endothelial cells (VECs) and encompasses the extracellular matrix and vascular physicochemical factors. The vascular wall microenvironment, comprising the vasa vasorum (VV) and their distinctive stem/progenitor cell niches, represents a pivotal site implicated in vascular inflammation and pathological remodeling. Additionally, the perivascular microenvironment, comprising perivascular adipose tissue (PVAT), contains adipocytes and stem cells that may contribute to the pathological process of atherosclerosis (AS).

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  FIGURE 3. Liver sinusoidal endothelial cells (LSECs) in hepatic regeneration and fibrosis following liver Injury. During early liver injury, upregulated CXC-chemokine receptor 7 (CXCR7) and downregulated Ang2 in LSECs, increase hepatocyte growth factor (HGF) and Wnt-2, reduce transforming growth factor-β (TGF-β), creating a pro-regenerative microenvironment. Later, Ang2 upregulation enhances vascular endothelial growth factor receptor-2 (VEGFR-2), forming a pro-angiogenic microenvironment. Persistent fibroblast growth factor receptor 1 (FGFR1) signaling boosts CXCR4 and TGF-β, inducing a pro-fibrotic microenvironment. After hepatectomy, LSECs secrete stromal cell-derived factor 1 (SDF1) to recruit bone marrow CXCR7 (+) progenitors of liver sinusoidal endothelial cells (sprocs), which differentiate into LSECs. In CCl4-induced liver injury, hypoxia-inducible factor-1α (HIF-1α) elevates CXCR4 and platelet-derived growth factor-BB (PDGF-BB), inhibits CXCR7, while PDGF-BB activates hepatic stellate cells (HSCs), promoting a pro-fibrotic microenvironment.

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  FIGURE 4. Involvement of the vascular microenvironment in the development of atherosclerosis (AS). The vasa vasorum (VV) in the vascular microenvironment is a conduit for the delivery of macrophages and inflammatory factors. Cytokines secreted by fibroblasts promote VV expansion and neogenesis, while the high permeability of the neovascularized VV can lead to lipid deposition and plaque formation. In addition, stem progenitor cells in the “angiogenic zone” of the VV and perivascular adipose tissue (PVAT) can differentiate into smooth muscle cells (SMCs), which are involved in vascular remodeling, both of which may lead to the development of AS.